In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis
In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis
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DOI：
10.1093/brain/awx247
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发表时间：
2017-11-01
期刊：
影响因子：
14.5
通讯作者：
Mainero, Caterina
中科院分区：
文献类型：
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作者：
Granberg, Tobias;Fan, Qiuyun;Mainero, Caterina
神经轴突病理是多发性硬化症疾病进展的主要决定因素；然而，其潜在的病理生理机制，包括其与炎性脱髓鞘的联系以及在疾病过程中的暂时发生，仍不清楚。我们使用超高场(7T)、超高梯度强度扩散和T-1/T-2加权髓鞘敏感磁共振成像来表征早期多发性硬化症患者皮质和白质髓鞘和神经轴突完整性的微结构变化，它们在皮损和正常组织中的分布，以及它们与神经功能障碍的相关性。26例早期多发性硬化症患者(病程45年)和24例年龄匹配的健康对照组接受了7T T-2加权成像用于皮质病变分割，3T T-1/T-2加权髓鞘敏感成像和轴突定向弥散和密度成像用于评估皮质和白质皮损和正常组织中髓鞘、轴突和树突的微结构完整性。为了进行比较，还评估了传统的平均扩散系数和分数各向异性指标。92%的早期多发性硬化症患者存在皮质病变，其特点是细胞内体积分数较低(配对t检验P=0.015)，髓鞘敏感性对比度较低(相关样本Wilcoxon符号等级检验P=0.030)，平均弥散率(相关样本Wilcoxon符号等级检验P=0.022)高于对侧外观正常的皮质。与正常白质相比，白质病变的表现相似(均P
Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T-1/T-2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration 45 years) and 24 age-matched healthy controls underwent 7T T-2*-weighted imaging for cortical lesion segmentation and 3T T-1/T-2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P